Development of a high resolution melting method for the detection of genetic variations in hypertrophic cardiomyopathy.
Clin Chim Acta
; 411(23-24): 1983-91, 2010 Dec 14.
Article
em En
| MEDLINE
| ID: mdl-20800588
ABSTRACT
BACKGROUND:
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease affecting 1 in 500 people. Due to large cohorts to investigate, the number of disease-causing genes, the size of the 2 prevalent mutated genes, and the presence of a large spectrum of private mutations, mutational screening must be performed using an extremely sensitive and specific scanning method.METHODS:
High Resolution Melting (HRM) analysis was developed for prevalent HCM-causing genes (MYBPC3, MYH7, TNNT2, and TNNI3) using control DNAs and DNAs carrying previously identified gene variants. A cohort of 34 HCM patients was further blindly screened. To evaluate HRM sensitivity, this cohort was also screened using an optimized DHPLC methodology.RESULTS:
All gene variants detected by DHPLC were also readily identified as abnormal by HRM analysis. Mutational screening of a cohort of 34 HCM cases led to identification of 19 mutated alleles. Complete molecular investigation was completed two times faster and cheaper than using DHPLC strategy.CONCLUSIONS:
HRM analysis represents an inexpensive, highly sensitive and high-throughput method to allow identification of mutations in the coding sequences of prevalent HCM genes. Identification of more HCM mutations will provide new insights into genotype/phenotype relationships and will allow a better knowledge of the HCM physiopathology.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Cardiomiopatia Hipertrófica
/
Congelamento
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Clin Chim Acta
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
França